(a) Field of the Invention
The invention relates to pharmaceutical compositions based on the use of "Aframomum" seeds to solve the problem of male erectile dysfunction as well as premature ejaculation in men.
(b) Description of Prior Art
Mechanisms of erection
The penis is composed of a mass of erectile tissue enclosed in three cylindrical fibrous compartments. Penile erection is a haemodynamic event under autonomic nervous control. During the change from the flaccid condition of the organ to its erect state, there is increased blood flow filling the vascular spaces which results in tumescence. It is generally accepted that vasodilatation of the penile arteries rapidly followed by relaxation of the cavernous smooth muscle are primarily responsible for the initiation of erection (Newman and Northup, 1981, Urol., 17:399-408).
There has been considerable progress in the understanding of the nervous control of the penile vasculature. Many neuropeptides including noradrenaline (NA), acetylcholine (ACh), adenosine 5'-triphosphate (ATP), serotonin 5-hydroxytryptamine (5-HT), as well as vasoactive intestinal polypeptide (VIP), calcitonin gene-related peptide (CGRP), neuropeptide Y (NPY), and substance P (SP), have been localized in perivascular nerves and considered as neurotransmitter candidates.
Causes of erectile dysfunction
Erectile dysfunction or impotence is common, affecting an estimated one in ten men, with prevalence much higher in certain subgroups: diabetics, smokers (Kaiser, 1988, Am. J. Med., 85:147-152). It appears to be an age-related disorder with an incidence of 1.9% at the age of 40 and 25% at the age of 65 (Krane et al, 1989, N. Engl. J. Med., 321:1648-1659).
The most common causes of impotence are generally classified as being of vascular, endocrine, neurological and psychogenic nature, but most often the exact mechanisms involved are not known. There is frequently an overlap between aetiologies, such as in diabetic patients who have both vascular and neurological complications contributing to impotence. Furthermore, there is often a psychogenic component in patients with a distinct organic cause of impotence.
Drug therapy of erectile dysfunction
Endocrinal causes of impotence, constituting less than 10% of total causes of impotence, can be successfully treated by medical therapy. In all other causes, drug therapy has not been satisfactory and a few drugs and/or drug combinations have gained clinical acceptance. These drugs are vasodilators, they include yohimbine, papaverine, papaverine and phentolamine in combination and prostaglandin El.
Yohimbine and phentolamine are known to be an alpha-adrenoreceptor blocker. Yohimbine is available for oral use. It has first appeared to have promising value but recently, several studies revealed a marginal and non significant effect (Morales et al., 1987, J. Urol., 137:1168-72; Susset et al., 1989, J. Urol., 141:1360-1363). Furthermore, yohimbine may induce hypertension, rashes and panic attacks. It is important to note that yohimbine is not licensed in the United Kingdom and has never been approved by the United States FDA (January 1995, In La Lettre Medicale, Vol. 18, No. 20:89).
Papaverine is often characterized as a non-specific vasodilator, and its cellular mechanism of action is unclear. It is an intracorporeally administered drug and its efficiency is better than yohimbine. However, it is well known that an intracavernosal injection of papaverine can produce major side effects such as prolonged painful erection. Other side effects include fibrosis and bruising at the site of injection and liver function abnormalities among others (Virag, 1982, Lancet, vol. ii:938). Moreover, many patients are disenchanted with the long-term injection involved in intracavernosal pharmacotherapy, finding the technique artificial, lacking in spontaneity and being time consuming.
Prostaglandin E1 (PGE1) is also administered intracavernosally. Some studies have shown PGE1 to be as effective as papaverine or the papaverine/phentolamine combination (Earle et al, 1990, J. Urol., 143:57-59), but like papaverine and yohimbine it also causes undesirable effects including local pain and prolonged erection.
It would be highly desirable to be provided with a painless therapy for male erectile dysfunction as well as for premature ejaculation in male without the drawbacks of the prior art techniques.